Pediatric severe traumatic brain injury (TBI) is the leading cause of death and disability in children ages 1-14 years old. There are no effective therapies to treat secondary brain injury. Pre-clinical and Phase I clinical progenitor cell therapies have shown promise in TBI/stroke. This proposed study is a follow-up trial from a previously performed Phase I trial (IND BB12620/NCT00254722) that demonstrated the safety and potential CNS structural preservation effect of intravenous autologous bone marrow mononuclear cells (BMMNC) after severe TBI in children. Pre-clinical data suggest that BMMNCs alter the global neuroinflammatory response to traumatic brain injury, serving to preserve injured/at-risk neurons that would otherwise die. Functional improvement has been demonstrated in two animal models of CNS injury: TBI and stroke. Further, structural integrity/preservation is associated with improved functional outcomes. For these reasons, a cell based therapeutic approach is proposed. Autologous cells eliminate the possibility of rejection, and obviate the need for anti- rejection medications. The purpose of this study is to determine the effect of intravenous infusion of autologous BMMNCs on brain structure and neurocognitive/functional outcomes after severe TBI in children. The study is designed as a prospective, randomized, placebo controlled blinded, Phase 2 safety/biological activity study. [A Bayesian adaptive dose escalation design is planned to assess doses of 6 X106 and 10 X106 cells/kg body weight vs. placebo. Aim 1: Determine the effect of autologous BMMNC on CNS white matter (WM), gray matter (GM) structural preservation. Volumetric and DTMRI will be performed acutely (first clinically stable time point), and at one month, 6 (primary outcome) and 12 months (safety) post-injury. Quantitative indices of both macro- and microscopic integrity (e.g. volume and fractional anisotropy/mean diffusivity) will be evaluated over time and compared to baseline measurements (immediate post- injury) and non-treated controls. Aim 2: Determine if autologous BMMNC infusion preserves structural integrity of GM and WM regions of interest [and improves functional and neurocognitive deficits in children after TBI.] We will examine the effect of BMMNC infusion on 1) FA and MD in regions of interest in WM and GM, and 2) specific global, adaptive behavior, psychological health, and neuropsychological outcomes. Aim 3: Determine if autologous BMMNC infusion reduces the neuroinflammatory response to TBI. CNS inflammation will be determined by plasma: CSF ratios of albumin (surrogate for micro vascular permeability), IL-1a, IL-4, Tonga, IL-6, and IL-10, measured every 12 hours for the first 7 days post-injury.